Safety and Efficacy of Sofosbuvir/GS-5885 Fixed-Dose Combination (FDC) +/-Ribavirin in HCV Genotype 1 Subjects - Full Text View

Purpose

The purpose of this study is to evaluate the safety, tolerability and antiviral efficacy of sofosbuvir/GS-5885 (FDC) with or without RBV administered for 8 or 12 weeks of treatment in subjects with chronic genotype 1 HCV infection who are treatment-naïve and for 12 weeks in subjects who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

Condition	Intervention	Phase
Chronic Hepatitis C Virus	Drug: Sofosbuvir/GS-5885 400/90 mg Drug: Ribavirin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed Dose Combination +/- Ribavirin in Subjects With Chronic Genotype 1 HCV Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Sustained virologic response after discontinuation of therapy [ Time Frame: 12 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
Sustained virologic response (SVR) 12 weeks after the end of treatment (SVR12 defined as HCV RNA < lower limit of quantification [LLOQ] 12 weeks after last dose of study drug).
Safety and tolerability of combination treatment with sofosbuvir (SOF)/GS-5885 fixed-dose combination (FDC) +/- RBV as measured by review of the accumulated safety data. [ Time Frame: Safety and tolerability on treatment and 30 days post last dose. ] [ Designated as safety issue: Yes ]
Frequency and severity of adverse events.

Secondary Outcome Measures:

Sustained virologic response after discontinuation of therapy. [ Time Frame: 2,4,8, and 24 weeks after discontinuation of therapy ] [ Designated as safety issue: No ]
Sustained virologic response (SVR) at 2,4,8, and 24 weeks after discontinuation of therapy (SVR 2, SVR4, SVR 8, and SVR24 defined as HCV RNA < lower limit of quantification [LLOQ] after last dose of study drug).
Viral resistance to sofosbuvir and GS-5885 combination therapy during and after treatment. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
To evaluate the emergence of viral resistance to sofosbuvir and GS-5885 during treatment and after treatment discontinuation
Characterization of viral dynamics during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
To characterize viral dynamics during treatment and after treatment discontinuation.
Characterization of steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
To characterize steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation.

Estimated Enrollment:	100
Study Start Date:	October 2012
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sofosbuvir/GS-5885 for 8 wks in Tx-naïve subjects	Drug: Sofosbuvir/GS-5885 400/90 mg FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Sofosbuvir/GS-5885 + RBV for 8 wks in Tx-naïve sub	Drug: Sofosbuvir/GS-5885 400/90 mg FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977. Drug: Ribavirin RBV (1000 or 1200 mg/day divided BID)
Experimental: Sofosbuvir/GS-5885 for 12wks in Tx-naïve subjects	Drug: Sofosbuvir/GS-5885 400/90 mg FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Sofosbuvir/GS-5885 for 12 wks in PI-exp subjects	Drug: Sofosbuvir/GS-5885 400/90 mg FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977.
Experimental: Sofosbuvir/GS-5885 + RBV for 12 wks in PI-exp subjects	Drug: Sofosbuvir/GS-5885 400/90 mg FDC tablet (SOF 400 mg/GS-5885 90 mg) once daily Other Name: Sofosbuvir is also known as GS-7977 or PSI-7977. Drug: Ribavirin RBV (1000 or 1200 mg/day divided BID)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age equal to or greater than 18 years, with chronic genotype 1 HCV infection
HCV RNA equal to or greater than 10,000 IU/mL at Screening
Cirrhosis determination; a liver biopsy may be required
Screening laboratory values within defined thresholds
Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

Pregnant or nursing female or male with pregnant female partner
Current or prior history of clinical hepatic decompensation
Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain -resolved skin cancers)
Chronic use of systemic immunosuppressive agents
History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01726517

Locations

United States, Texas

San Antonio, Texas, United States, 78215

Sponsors and Collaborators

Gilead Sciences

More Information

No publications provided

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01726517 History of Changes
Other Study ID Numbers:	GS-US-337-0118
Study First Received:	November 10, 2012
Last Updated:	May 10, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

HCV genotype 1 (GT-1)
HCV
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
GS-7977
GS-5885

Ribavirin
Open Label
Sofosbuvir
Treatment-Naïve
Protease Inhibitors
PI

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections

Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 17, 2013